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Nucleic Acids Res. 2017 Jan 9;45(1):435-445. doi: 10.1093/nar/gkw745. Epub 2016 Aug 27.

Reactive sulfur species regulate tRNA methylthiolation and contribute to insulin secretion.

Author information

1
Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
2
Department of Oral and Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
3
Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST), Kawaguchi, Japan.
4
Dojindo Laboratories, 2025-5 Tabaru Kamimashikigun, Mashikimachi, Kumamoto 861-2202, Japan.
5
Department of Health Chemistry, Showa Pharmaceutical University, Tokyo 194-8543, Japan.
6
Department of Microbiology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556,Japan.
7
Department of Environmental Health Sciences and Molecular Toxicology,Tohoku University Graduate School of Medicine, Sendai 980-8577, Japan.
8
Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan tomikt@kumamoto-u.ac.jp.

Abstract

The 2-methylthio (ms2) modification at A37 of tRNAs is critical for accurate decoding, and contributes to metabolic homeostasis in mammals. However, the regulatory mechanism of ms2 modification remains largely unknown. Here, we report that cysteine hydropersulfide (CysSSH), a newly identified reactive sulfur species, is involved in ms2 modification in cells. The suppression of intracellular CysSSH production rapidly reduced ms2 modification, which was rescued by the application of an exogenous CysSSH donor. Using a unique and stable isotope-labeled CysSSH donor, we show that CysSSH was capable of specifically transferring its reactive sulfur atom to the cysteine residues of ms2-modifying enzymes as well as ms2 modification. Furthermore, the suppression of CysSSH production impaired insulin secretion and caused glucose intolerance in both a pancreatic β-cell line and mouse model. These results demonstrate that intracellular CysSSH is a novel sulfur source for ms2 modification, and that it contributes to insulin secretion.

PMID:
27568003
PMCID:
PMC5224495
DOI:
10.1093/nar/gkw745
[Indexed for MEDLINE]
Free PMC Article

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